E6 oncoproteins from cancer associated Human Papillomaviruses (HPV) associate with a subset of cellular proteins that contain PDZ motifs. Genetic evidence has shown that the interaction of E6 with cellular PDZ proteins is necessary for both full HPV virus replication in human keratinocytes and transformed phenotypes in mouse squamous cells. As several different complexes of cellular proteins interact with E6 via PDZ interactions, the significance of particular PDZ containing targets of E6 is not defined. We have used a proteomics approach to identify complexes of cellular proteins that interact with cancer associated E6 oncoproteins. This has identified novel complexes of cellular proteins that interact with E6 by PDZ ligand interactions. The purpose of this application is to characterize the PDZ complexes we have identified, and to explore the biological significance of E6-PDZ protein interactions.